Traumatic Stress and Alcohol Problems: Between- and Within- Person Associations

描述(申请人提供)：本申请是对PA-10-255《酒精依赖行为调控机制及相关表型》的响应，旨在促进对调控机制与酒精依赖之间的关联、导致酒精依赖风险的遗传和环境因素以及将酒精依赖与相关外化行为区分开来的因素的研究。伊拉克自由行动/持久自由退伍军人行动的拟议研究利用纵向爆发式设计来模拟创伤后应激障碍症状、酒精依赖和相关行为问题的动态过程。我们测试了关于潜在的调控缺陷、依赖和其他外化行为之间的分离以及基因x环境交互作用的假设。创伤后应激障碍与酒精依赖以及导致社会和职业功能困难的相关外化问题有关(Frueh等人，2001年；Hog等人，2007年；Mills等人，2007年；Seal等人，2011年)。研究表明，影响行为调节的缺陷是将创伤后应激障碍和酒精相关问题联系在一起的两条截然不同的途径(Miller等人，2006年)。我们认为这两条途径与不同类型的问题有关。最近关于物质依赖的负强化模型的理论和研究强调了情绪不稳定而不是平均水平的负面情绪在依赖发展中的作用(Baker等人，2004；Simons等人，2009,2010b；Weinstein等人，2008)。创伤后应激障碍与明显的不稳定有关，我们假设正是这种情绪的变异性增加了这一人群发展成酒精依赖的风险。相反，我们认为与创伤后应激障碍和酒精使用相关的行为问题是行为去抑制的功能。去抑制调节创伤后应激障碍和酒精问题之间的联系(Miller等人，2006年)，去抑制主要与酒精相关的行为问题有关，而不是依赖症状(Simons等人，2009年；2010b)。虽然创伤暴露与创伤后应激障碍和酒精问题的发展有关，但这些联系在不同的人之间存在显著的差异。我们假设5-羟色胺转运体连锁多态区域(5-HTTLPR)的基因型与创伤暴露相互作用，以预测创伤后应激障碍症状和酒精依赖，以及影响稳定性和行为去抑制的中间变量。这项研究将测试监管机制的作用 随着时间的推移，症状的增长，通过个人x情境影响的结果的急性变化，并测试饮酒对不稳定和创伤后应激障碍症状的交互影响。通过整合对遗传和环境风险、基本行为调节缺陷、酒精依赖和相关条件的评估，该研究可以提高我们对病因、风险和弹性机制以及治疗变化的潜在机制的理解。

DESCRIPTION (provided by applicant): This application is in response to PA-10-255 "Behavioral Regulation Mechanisms of Alcohol Dependence and Related Phenotypes", which seeks to promote research on associations between regulation mechanisms and alcohol dependence, genetic and environmental factors conferring risk for alcohol dependence, and factors differentiating alcohol dependence from related externalizing behaviors. The proposed study of Operation Iraqi Freedom / Operation Enduring Freedom veterans utilizes a longitudinal burst design to model the dynamic course of PTSD symptoms, alcohol dependence, and associated conduct problems. We test hypotheses regarding underlying regulatory deficits, dissociation between dependence and other externalizing behaviors, and gene x environment interactions. PTSD is related to alcohol dependence as well as associated externalizing problems resulting in difficulties in social and occupational functioning (Frueh, et al., 2001; Hog et al., 2007; Mills et al., 2007; Seal et al., 2011). Research indicates that deficits in affect an behavioral regulation are two distinct pathways linking PTSD and alcohol-related problems (Miller et al., 2006). We propose that these two pathways are associated with different types of problems. Recent theory and research on negative reinforcement models of substance dependence have highlighted the role of affect lability, rather than mean levels of negative affect, in the development of dependence (Baker et al., 2004; Simons et al., 2009, 2010b; Weinstein et al., 2008). PTSD is associated with marked lability, and we posit that it is this variability in mood that confers risk for the development of alcohol dependence in this population. In contrast, we propose that conduct problems associated with PTSD and alcohol use are a function of behavioral disinhibition. Disinhibition mediates associations between PTSD and alcohol problems (Miller et al., 2006) and disinhibition is primarily associated with alcohol-related conduct problems rather than dependence symptoms (Simons et al., 2009; 2010b). Although trauma exposure is associated with the development of PTSD and alcohol problems, there is significant variability in these associations across persons. We hypothesize genotype at the serotonin transporter linked polymorphic region (5-HTTLPR) interacts with trauma exposure to predict PTSD symptoms and alcohol dependence, as well as the intermediary variables, affect lability and behavioral disinhibition. The study will test the role of regulation mechanisms in growth of symptoms over time, acute changes in the outcomes via person x situation effects, and test reciprocal effects of alcohol consumption on lability and PTSD symptoms. By integrating assessment of genetic and environmental risk, basic behavioral regulation deficits, and alcohol dependence and related conditions the study can improve our understanding of etiology, risk and resilience mechanisms, and potential mechanisms of therapeutic change.